Background: Objective: This study aimed to analyze the effect of helminth exposure on T cell activation in a T and B cell co-culture system. Methods: T and B cells were isolated from healthy donor blood, stimulated with aCD3/aCD28, and exposed to Results: B cells reduced T cell proliferation, and SM exposure partly attenuated this inhibitory effect on CD4 T cells. ASC exposure did not affect T cell proliferation but increased soluble IL-15Rα and surface IL-15Rα and IL-2/15Rβ on CD4 T cells. Restimulation with recombinant human IL-15 revealed reduced and unsustained STAT5 activation in CD4 and CD8 T cells in ASC-exposed co-cultures. Additional analysis showed altered phosphorylation of STAT1, STAT3, and STAT6, indicating broader impairment of IL-15 responsiveness and a dampened Th1 activation profile. BCL6/BLIMP-1 transcription factor expression of B cells in ASC-exposed co-cultures suggested a shift toward a more differentiated phenotype, such as plasma cell, memory B cells, or marginal zone MZ B cells, which are all typically BCL6 Conclusion: ASC antigen exposure modulates T cell activation through dynamic regulation of the IL-15-pathway and STAT signaling. These findings suggest that ASC exposure may help prevent prolonged IL-15-driven responses, potentially limiting excessive inflammation during TB. B cells in ASC-exposed co-cultures exhibit transcriptional changes consistent with a shift away from the germinal center phenotype toward more differentiated states.